CircINTS4 Facilitates Chemoresistance of TNBC by Competitively Binding miR-129-5p/POM121 Axis

Abstract

Objectives. To detect the expression of circular RNA (circRNA) circINTS4 in triple-negative breast cancer (TNBC) and to analyze the relationship between the expression of circRNA circINTS4 and the clinicopathological characteristics and chemotherapy resistance of patients with TNBC. Methods. Bioinformatics was used to predict that circINTS4 and POM121 could bind to miR-129-5p, and dual luciferase reporter genes proved that circINTS4 could bind to miR-129-5p and miR-129-5p could bind to POM121. RNA immunoprecipitation (RIP) and RNA pull-down experiments confirmed that circINTS4 binds to miR-129-5p. The correlation among circINTS4, miR-129-5p, and POM121 was detected by qRT-PCR. Results. In ADR-resistant TNB cells, circINTS4 was significantly up-regulated, miR-129-5p was down-regulated, and POM121 protein expression was significantly up-regulated. Experimental results showed that circINTS4 knockdown inhibited proliferation, migration, invasion, and autophagy. Knocking down miR-129-5p or overexpression of POM121 reversed the inhibitory effect of sh-circints4 on the development of ADR-resistant TNBC cells. In addition, CIRCINTS4 regulates POM121 expression by sponge-adsorbed miR-129-5p. CIRCINTS4 knockdown prevents ADR-resistant tumor growth by regulating the miR-129-5p/POM121 axis in vivo. Conclusions. CircRNA circINTS4 may act as the ceRNA of miR-129-5p to regulate the expression of target gene POM121, thereby promoting the progress of TNBC molecular mechanism and providing scientific basis for circINTS4 as a new molecular target for clinical diagnosis and drug resistance therapy of TNBC.

Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor

“…The limited choices of medical treatment for them are usually chemotherapy and immunotherapy but with limited therapeutic effect. Therefore, there is still a tremendous unmet need for the development of novel therapeutics for TNBC [ 6 ].…”

Circular RNAs in the chemoresistance of triple‐negative breast cancer: A systematic review

“…There were three studies published in 2019 (Liang et al, 2019; Ma et al, 2019; Yang et al, 2019), five studies published in 2020 (Dou et al, 2020a; Liu et al, 2020; Yang et al, 2020; Zang et al, 2020; Zhang, Su, et al, 2020), 10 studies published in 2021 (Hao et al, 2021; Huang et al, 2021; Li, Xia, et al, 2021; Li, Xu, et al, 2021; Ni et al, 2021; Wang, Liang, et al, 2021; Wang, Zhou, et al, 2021; Wu et al, 2021a; Zheng et al, 2021; Zhu et al, 2021a), eight studies published in 2022 (Chen, Shi, et al, 2021; Cui et al, 2022; Huang et al, 2022; Tang et al, 2022; Wang, Chen, et al, 2022; Wang, Shan, et al, 2022; Wang, Yang, et al, 2022; Xie & Zheng, 2022), and one study published in 2023 (Xu et al, 2023). Fourteen of the studies (Chen, Shi, et al, 2021; Cui et al, 2022; Dou et al, 2020a; Hao et al, 2021; Li, Xia, et al, 2021; Li, Xu, et al 2021; Liang et al, 2019; Tang et al, 2022; Wang, Chen, et al, 2022; Wang, Liang, et al, 2021; Wang, Shan, et al, 2022; Xie & Zheng, 2022; Xu et al, 2023; Zhang, Su, et al, 2020) were on adriamycin (ADM) resistance, nine studies (Huang et al, 2022; Li, Xu, et al, 2021; Liu et al, 2020; Ma et al, 2019; Ni et al, 2021; Wang, Zhou, et al, 2021; Yang et al, 2020; Zang et al, 2020; Zheng et al, 2021) were related to paclitaxel (PTX) resistance, two were related to 5‐fluorouracil (5‐FU) resistance (Yang et al, 2019; Zhu et al, 2021a), two studies were related to cisplatin resistance...…”

“…(Dou et al, 2020a;Liu et al, 2020;Yang et al, 2020;Zang et al, 2020;Zhang, Su, et al, 2020), 10 studies published in 2021(Hao et al, 2021;Huang et al, 2021;Li, Xu, et al, 2021;Ni et al, 2021;Wang, Liang, et al, 2021;Wang, Zhou, et al, 2021;Wu et al, 2021a;Zheng et al, 2021;Zhu et al, 2021a), eight studies published in 2022(Chen, Shi, et al, 2021;Cui et al, 2022;Huang et al, 2022;Tang et al, 2022;Wang, Chen, et al, 2022;Wang, Shan, et al, 2022;Xie & Zheng, 2022), and one study published in 2023(Xu et al, 2023). Fourteen of the studies(Chen, Shi, et al, 2021;Cui et al, 2022;Dou et al, 2020a;Hao et al, 2021;Li, Xu, et al 2021;Liang et al, 2019;Tang et al, 2022;Wang, Chen, et al, 2022;Wang, Liang, et al, 2021;Wang, Shan, et al, 2022;Xie & Zheng, 2022;Xu et al, 2023;Zhang, Su, et al, 2020) were on adriamycin (ADM) resistance, nine studies(Huang et al, 2022;Li, Xu, et al, 2021;Liu et al, 2020;Ma et al, 2019;…”

CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis

“… 27 Tang et al indicated that circINTS4 confers chemotherapy resistance in breast cancer via competitive binding miR-129-5p/POM121 signaling axis. 28 Moreover, Chen et al reported that CircSCAP interacts with SF3A3 to restrain the malignant progression of non-small cell lung cancer via activating p53 signaling. 29 circAGFG1 is a poorly studied circRNA, and no studies have been reported in ovarian cancer.…”